Our research program is concerned with the study of the pathogenesis of leukemia and the basic mechanisms involved in the suppression of the leukemic state. Our investigations into the murine virus (FLV)-induced erythroleukemia cell system continue. The cells can be induced to differentiate along the erythroid pathway when grown in the presence of DMSO or a variety of other inducers. Among the aspects to be studied in the differentiating cells are: 1) the mechanism of action of compounds which stimulate or inhibit differentiation; 2) the changes that occur in the cell membrane; 3) the modulation of gene expression; 4) DNA transcription and replication; and 5) cytoskeletal alterations. These studies have been designed to provide insight into the mechanisms underlying the neoplastic state. Elucidation of the regulatory mechanisms involved in the shift from malignancy to differentiation may yield information which will aid in the development of new chemotherapeutic agents.